Brain Stimulation for Torsion Dystonia

Abstract

Importance: Dystonia is a heterogeneous neurologic disorder characterized by abnormal muscle contractions for which standard medical therapy is often inadequate. For such patients, therapeutic brain stimulation is becoming increasingly used.

Objectives: To review the evidence and effect sizes for treating different types of dystonia with different types of brain stimulation and to discuss recent advances relevant to patient selection, surgical approach, programming, and mechanism of action.

Evidence review: PubMed was searched for publications on the clinical effect of brain stimulation in dystonia up through December 31, 2014. Recent meta-analyses, consensus statements, and evidence-based guidelines were incorporated. Emphasis was placed on deep brain stimulation (DBS) and randomized clinical trials; however, other stimulation modalities and trial designs were included. For each intervention the mean change in dystonia severity, number of patients studied, and evidence of efficacy based on American Academy of Neurology criteria were determined.

Findings: Strong (level B) evidence supports the use of DBS for the treatment of primary generalized or segmental dystonia, especially when due to mutation in the DYT1 gene, as well as for patients with cervical dystonia. Large effect sizes have also been reported for DBS treatment of tardive dystonia, writer's cramp, cranial dystonia, myoclonus dystonia, and off-state dystonia associated with Parkinson disease. Lesser benefit is generally seen in dystonia secondary to structural brain damage. Other brain stimulation techniques, including epidural cortical stimulation and noninvasive brain stimulation, have been investigated, but generally report smaller effect sizes in fewer patients.

Conclusions and relevance: Patients with dystonia that is not adequately controlled with standard medical therapy should be referred for consideration of DBS, especially patients with generalized, segmental, or cervical dystonia. Other less-invasive stimulation modalities require further research before being considered a therapeutic alternative.

Figure 1

Illustration of bilaterally implanted DBS devices. Each DBS device is comprised of a stimulating lead in the brain, extension cable, and programmable pulse generator, usually implanted in the chest (compliments of Medtronic, Inc.)

Figure 2

Deep brain stimulation target in the globus pallidus based on retrospective analysis of the site of effective electrode contacts and modeling of stimulation fields. MRI was used to identify the location of the DBS electrode in patients with DYT-1 dystonia (A) and co-registered into a common atlas space (B). The stimulation field for the effective electrode contact in each patient was modeled (C). A probabilistic volume in the posteroventral aspect of the GPi was identified that could be used to guide future electrode placement or programming (D-F). Modified with permission from Cheung et al. 2014 Annals of Neurology.

Figure 3

Evidence of Efficacy for Brain Stimulation in Dystonia. Each bubble represents the evidence that a particular type of brain stimulation is effective for a particular type of dystonia. The position of the bubble along the y axis reflects the average improvement in dystonia severity, the size of the bubble reflects the number of patients studied, and the bubble outline reflects the quality of the evidence assessed by AAN criteria (level B = black outline, level C = grey outline, level U = no outline). Treatments with the best evidence of efficacy have larger bubbles higher on the graph and outlined by darker lines. Abbreviations refer to the conditions as listed in Table 1.

Figure 4

Location and functional relationship between invasive and noninvasive brain stimulation sites in dystonia. The globus pallidus pars interna, the primary target of deep brain stimulation for dystonia, is shown in red (A). Resting state functional connectivity with this deep brain stimulation site identifies positive and negative correlations on the surface of the brain potentially amenable to noninvasive brain stimulation (B). Prior targets of noninvasive brain stimulation are identified including primary motor cortex (M1), dorsal premotor cortex (PMd) and supplementary motor area (SMA). Modified with permission from Fox et al. 2014 PNAS.